Using neural transplantation to replace lost cells in the brain and restore functions following TBI is a challenging but attractive strategy. To date, the few published studies investigating grafting of human neural cells have primarily utilized cells derived from fetal tissues or a human teratocarcinoma line (NT2 cell line). Despite some positive outcomes from these studies, however, cell source limitations, graft rejection and ethical controversies hinder their use in clinic. Recent studies show that the mature mammalian CNS harbors multipotent stem cells capable of differentiation into neurons and glia in various regions. These cells, when derived from the subventricular zone and the hippocampus, have been shown to be capable of generating new neurons that are able to integrate both anatomically and functionally into the existing neuronal circuitry and contribute to the maintenance of normal brain functions. These findings highlight the potential therapeutic value of adult derived neural stem and progenitor cells (NS/NPCs) in treating injured brain. Thus far, we and others have successfully isolated human NS/NPCs from neurosurgical resection tissues and established their long term culturing. Examination of these adult NS/NPCs as a potential candidate for neuronal cell replacement therapy, especially as a potential autologous cell source for TBI patients, is urgently needed. To date, very few studies have attempted to examine the behavior of adult human NS/NPCs in the injured mature CNS. In preliminary studies, we show that NS/NPCs derived from surgically removed tissues can survive in normal and injured rat brain after transplantation. However, it is not known whether these cells can survive for extended period in an injured environment and integrate into the host neuronal circuitry. We, therefore, plan to examine the long term fate of adult human NS/NPCs after transplantation into the injured brain. Thus, the overall focus of this proposal is aimed at exploring the long term survival and differentiation fate of transplanted adult human NS/NPCs in the injured rat brain, and to determine the extent to which these cells can integrate anatomically and functionally into the host neuronal circuitry and modify the functional recovery of the injured host. PUBLIC HEALTH RELEVANCE: To date, little information exists regarding the behavior, plasticity and fate of adult human neural stem cells after transplantation into the adult brain especially in an injured environment. This proposal is aimed at assessing the ability of survival, differentiation, anatomically and functionally integration of these cells into the adult host CNS following transplantation into normal and injured adult rat brain.